MECHANISMS UNDERLYING REDUCTION OF CLINICAL EVENTS IN LIPID-LOWERING TRIALS

OBJECTIVE: To outline the emerging hypotheses explaining the reductions in clinical events in trials of lipid lowering. DESIGN: Selective literature review. MAIN RESULTS: The primary angiographic end-points of recent lowering trials, justified largely from a hemodynamic paradigm of coronary disease, have been shown to improve significantly but modestly. The improvements appear out of keeping with the more impressive trends in reducing clinical events. There are many possible explanations for these results. Prominent among these is the influence of lipid lowering on the atherothrombotic and vasomotor processes, including endothelially mediated ones, which underlie both plaque rupture and plaque progression. Additionally; there is now a greater appreciation of constituents of plaques, especially moderate ones, in rendering lesions either susceptible or resistant to acute disruption. In aggregate, these newer areas of emphasis have led to the concept of plaque stabilization. CONCLUSIONS:Plaque stabilization is a new concept encompassing many functional and morphological factors that are influenced in the short and long term by aggressive lipid lowering. This concept may help explain reductions in clinical, events noted in lipid lowering trials.